Na ion , K ion-ATPase, an enzyme of the plasma membrane, is involved in the regulation of the internal ionic environment of most mammalian cells. Previous work has suggested that the inhibition of this enzyme by methylmercury may be related to the neurological abnormalities and the embryotoxic effects produced by this environmental poison. Our recent work shows that the interaction of methylmercury and other short-chain alkylmercury compounds with Na ion, K ion-ATPase leads to a unique mode of modification of this enzyme. While the overall Na ion plus K ion-dependent ATPAse activity of the mercurial-modified enzyme is inhibited, none of the partial reactions of the enzyme seem to be affected. In view of this, the goals of this project are: (1) To study in detail the mechanism of modifying effects of these mercurials on the isolated Na ion, K ion-ATPase. (2) To determine the functional consequences of the mercurial-induced modification of the enzyme. (3) To determine if the toxic effects of methylmercury in the intact animal are related to this unique type of modification of the enzyme. The purified dog kidney enzyme will be used to study the effects of mercurials on the kinetics of the partial reactions of the enzyme, and to identify the site of the reaction of the mercurials within the enzyme complex. Intact human red cells, and phospholipid vesicles containing the purified enzyme will be used to study the effects of mercurials on the Na ion, K ion-translocations that are mediated by the enzyme. Methylmercury-poisoned pregnant mice will be used to determine if the brain enzyme obtained from the mother and the fetus are affected in the same way that the purified enzyme is modified by methylmercury in vitro.